黑人和白人老年人的联合和个体线粒体 DNA 变异与认知结果。

Michelle C Odden, Yongmei Li, Vasantha Jotwani, Sylvie Dobrota, Annabel X Tan, Steven R Cummings, Michael G Shlipak, Rebecca Scherzer, Joachim H Ix, Marion S Buckwalter, Gregory J Tranah
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引用次数: 0

摘要

背景:线粒体功能障碍表现为神经退行性疾病和其他与年龄相关的疾病。在这项研究中,我们检测了两项大型老龄化研究中黑人和白人参与者的遗传线粒体 DNA(mtDNA)序列变异,以确定与认知功能相关的变异:参与者包括自我报告年龄≥ 70 岁的黑人和白人,他们参加了 "老年人生活方式干预和自立"(LIFE;N=1319)和 "健康老龄化和身体组成"(Health ABC;N=7888)研究。在 LIFE(3.6 年)和 Health ABC(10 年)的基线和随访期间,认知功能通过数字符号替换测试 (DSST) 和改良小型精神状态检查 (3MSE) 进行测量。我们使用序列核关联测试检验了 16 个线粒体功能区的多个变异对认知功能的联合影响。根据这些结果,我们使用混合效应模型对黑人和白人参与者中的常见变异进行了优先荟萃分析。结果显示,Bonferroni 调整后的 p 值为 0:复合体 I 的 ND1、ND2 和 ND5 亚基、12S RNA 和超变异区 (HVR) 的联合变异与基线 DSST 和 3MSE 显著相关。在对黑人参与者的荟萃分析中,ND1变异体m.4216T>C与3MSE下降较快有关联,HVR变异体m.462C>T与DSST下降较慢有关联。在白人参与者中,ND2变异体m.5460G>C与3MSE下降较慢有关,HVR变异体m.182C>T与3MSE下降较快有关:结论:在黑人和白人成年人中,氧化磷酸化复合物 I 变体与认知功能有关。
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Joint and Individual Mitochondrial DNA Variation and Cognitive Outcomes in Black and White Older Adults.

Background: Mitochondrial dysfunction manifests in neurodegenerative diseases and other age-associated disorders. In this study, we examined variation in inherited mitochondrial DNA (mtDNA) sequences in Black and White participants from 2 large aging studies to identify variants related to cognitive function.

Methods: Participants included self-reported Black and White adults aged ≥70 years in the Lifestyle Interventions and Independence for Elders (LIFE; N = 1 319) and Health Aging and Body Composition (Health ABC; N = 788) studies. Cognitive function was measured by the Digit-Symbol Substitution Test (DSST), and the Modified Mini-Mental State Examination (3MSE) at baseline and over follow-up in LIFE (3.6 years) and Health ABC (10 years). We examined the joint effects of multiple variants across 16 functional mitochondrial regions with cognitive function using a sequence kernel association test. Based on these results, we prioritized meta-analysis of common variants in Black and White participants using mixed effects models. A Bonferroni-adjusted p value of <.05 was considered statistically significant.

Results: Joint variation in subunits ND1, ND2, and ND5 of Complex I, 12S RNA, and hypervariable region (HVR) were significantly associated with DSST and 3MSE at baseline. In meta-analyses among Black participants, variant m.4216T>C, ND1 was associated with a faster decline in 3MSE, and variant m.462C>T in the HVR was associated with a slower decline in DSST. Variant m.5460G>C, ND2 was associated with slower and m.182C>T in the HVR was associated with faster decline in 3MSE in White participants.

Conclusions: Among Black and White adults, oxidative phosphorylation Complex I variants were associated with cognitive function.

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